Diarrhea causes a billion illness episodes and 2.5 million deaths/year in children under the age of 5 years in the developing world and China, making it the second most frequent cause of death in this age group. Despite this burden of disease, the clinical management of diarrhea has remained largely stagnant since the development of oral rehydration therapy over thirty years ago. Multiple small studies have demonstrated the efficacy of probiotic agents, or beneficial bacteria used to colonize the gut, for improving the clinical course of diarrheal illness in children. However limitations of these small studies, done in areas where diarrhea is caused predominantly by viral pathogens in well nourished children, limit the relevance of these studies in areas where diarrhea remains a serious threat to child health. We propose to evaluate the relative efficacy of Lactobacillus GG (LGG) and Bifidobacterium bifidum (Bb), two promising probiotic agents, in a randomized double-blinded placebo-controlled trial for the treatment of diarrhea at the community level in Santa Clara, a town in the Peruvian Amazon where chronic malnutrition and childhood diarrhea are highly endemic. Six hundred and fifty children ages 6 months to 6 years will be randomized to 3 groups, which will receive LGG, Bb, or placebo respectively for 5 days with each episode of diarrhea during the surveillance period. Diarrhea stool specimens will be examined for bacterial, viral, and parasitic pathogens. Our multiyear study will allow for the evaluation of treatment with these probiotic agents for all causes of diarrhea and on specific prevalent causes of pediatric diarrhea such as rota virus, enterotoxigenic E. coli, Shigella, Giardia and Campylobacter. Episode-specific outcomes such as time to last unformed stool, and subject-specific outcomes, including overall burden of disease, frequency of adverse events, and changes in nutritional status overtime, will be compared between treatment groups. Intensive study of a longitudinal cohort with stringent monitoring of adverse events will allow us to address many unanswered questions, such as the impact of breastfeeding and malnutrition on therapeutic efficacy and strategies for acceptance of the new therapies. The proposed project will allow for a critical and thorough evaluation of the efficacy, practicality, and safety of probiotic organisms in a developing country, where children continue to suffer high burdens of diarrheal diseases and are in need of new and improved approaches to treatment. [unreadable] [unreadable] [unreadable]